Importance of leukocytes in diabetes is based on the evidence that the bacterial infection occurs with h igh prevalence in patients with diabetes and the recent report that neutrophils exposed in a high glucose environment adhere to the surface of endothelial cells of retinal capillaries. Because it has been established th the accumulation of excess sugar alcohol sorbitol initiates various diabetic complications such as cataract formation and retinopathy, the reduced form of nicotinamide -adenine dinucleotide phosphate (NADPH)-dependent reductases and polyol formation in dog leukocytes was investigated. Both polymorphonuclear leukocytes (PMNs) and mononuclear cells (MNCs) contain three NADPH-dependent reductases: aldose reductase, aldehyde reductase, and glyceraldehyde reductase, with aldehyde reductase dominant. Despite the extremely low level of aldose reductase, glucose was metabolized into fructose through sorbitol in both PMNs and MNCs. However, the accumulation of sugar alcohols appeared to occur more in MNCs than PMNs. Dogs fed with galactose diet displayed accumulation of galactitol in both PMNs and MNCs. This galactosemic dog model also developed the leukocyte dysfunctions such s the impaired NADPH oxidase induction of neutrophils and the decreased lymphocyte blast formation that are reported with human diabetics.